Predictors of time to initiation of symptomatic therapy in early Parkinson's disease

Abstract

ObjectiveTo determine clinical and biological variables that predict time to initiation of symptomatic therapy in de novo Parkinson's disease patients.MethodsParkinson's Progression Markers Initiative is a longitudinal case–control study of de novo, untreated Parkinson's disease participants at enrolment. Participants contribute a wide range of motor and non‐motor measures, including biofluids and imaging biomarkers. The machine learning method of random survival forests was used to examine the ability of baseline variables to predict time to initiation of symptomatic therapy since study enrollment (baseline).ResultsThere were 423 PD participants enrolled in PPMI and 33 initial baseline variables. Cross‐validation results showed that the three‐predictor subset of disease duration (time from diagnosis to enrollment), the modified Schwab and England activities of daily living scale, and the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) total score modestly predicted time to initiation of symptomatic therapy (C = 0.70, pseudo‐R 2 = 0.13). Prediction using the three variables was similar to using the entire set of 33. None of the biological variables increased accuracy of the prediction. A prognostic index for time to initiation of symptomatic therapy was created using the linear and nonlinear effects of the three top variables based on a post hoc Cox model.InterpretationOur findings using a novel machine learning method support previously reported clinical variables that predict time to initiation of symptomatic therapy. However, the inclusion of biological variables did not increase prediction accuracy. Our prognostic index constructed, based on the group‐level survival curve can provide an indication of the risk of initiation of ST for PD patients based on functions of the three top predictors.

Artificial Intelligence-Based Clustering and Characterization of Parkinson’s Disease Trajectories

“…3 ), and the ‘OFF’-state UPDRS 3 score data ( Fig. S11 ), in which patients were examined at least 6 hours after the last dose, which is considered sufficient time for washing off the effect of levodopa or dopamine agonists [18]. Methodological details and statistical plots can be found in Supplementary Section S6 .…”

Linear predictive coding electroencephalography algorithms predict mortality in Parkinson’s disease

“… Highlights clinical and biomarker predictors for long-term survival risks. Yunliang Tang et al, 2021 [20] Multivariate Cox regression using two PD cohorts (training and validation); development of a nomogram and web-based survival calculator Age, PD duration, Hoehn-Yahr (HY) stage Achieved 4-, 6-, and 8-year AUCs of 0.716–0.814 in training, and 0.850–0.924 in validation; created a publicly accessible tool for survival estimation Provided a clinically practical model to estimate long-term mortality risk based on readily available clinical variables Wang et al, 2020 [23] EEG analysis of spectral features and complexity β and δ frequency bands EEG abnormalities correlate with cognitive decline Demonstrated EEG’s potential as a cognitive and motor biomarker Bäckström et al, 2018 [21] Longitudinal cohort study with multimodal assessments Cognitive impairment (Mini-Mental State Examination [MMSE] < 26), CSF amyloid-β42 AUC: 0.86; 10-year dementia risk stratification Developed a cerebrospinal fluid (CSF)-based model to predict dementia as a risk factor for mortality Simuni et al, 2016 [24] Predictive modeling of symptomatic therapy initiation Age, Unified Parkinson’s Disease Rating Scale (UPDRS) III motor score, olfactory dysfunction Delayed motor progression associated with predictors Showed clinical predictors for disease progression relevant to life expectancy …”

Isradipine plasma pharmacokinetics and exposure–response in early Parkinson’s disease

“…Time-to-initiation of antiparkinson therapy is a measure of increasing disease burden, and is manifested by a level of disability sufficient to require initiation of therapy. [20][21][22][23][24][25] In STEADY-PD III, individual need for symptomatic treatment was assessed through standard questionnaire by the site investigator that assessed one's function or current daily activities. There are some neuroimaging data to suggest this milestone-based outcome measure relates to underlying pathophysiologic changes of disease progression.…”

“…Clinical significance of this finding in absence of an impact on measures of motor and nonmotor disability remains to be determined. Time‐to‐initiation of antiparkinson therapy is a measure of increasing disease burden, and is manifested by a level of disability sufficient to require initiation of therapy 20–25 . In STEADY‐PD III, individual need for symptomatic treatment was assessed through standard questionnaire by the site investigator that assessed one’s function or current daily activities.…”